Hydrochloric Acid → Nilotinib Hydrochloride Anhydrous

HRID 2046435Notes

Reaction equation

HRID 2046435 reaction equation
[CH3:1][C:2]1[CH:3]=[CH:4][C:5]([C:21]([NH:23][C:24]2[CH:25]=[C:26]([C:36]([F:39])([F:38])[F:37])[CH:27]=[C:28]([N:30]3[CH:34]=[N:33][C:32]([CH3:35])=[CH:31]3)[CH:29]=2)=[O:22])=[CH:6][C:7]=1[NH:8][C:9]1[N:10]=[CH:11][CH:12]=[C:13]([C:15]2[CH:16]=[CH:17][CH:18]=[N:19][CH:20]=2)[N:14]=1.[ClH:40]>C(O)C>[CH3:1][C:2]1[CH:3]=[CH:4][C:5]([C:21]([NH:23][C:24]2[CH:25]=[C:26]([C:36]([F:38])([F:39])[F:37])[CH:27]=[C:28]([N:30]3[CH:34]=[N:33][C:32]([CH3:35])=[CH:31]3)[CH:29]=2)=[O:22])=[CH:6][C:7]=1[NH:8][C:9]1[N:10]=[CH:11][CH:12]=[C:13]([C:15]2[CH:16]=[CH:17][CH:18]=[N:19][CH:20]=2)[N:14]=1.[ClH:40]

Participants

4

Reactant 2

HCID 313Hydrochloric AcidHCID 644241Nilotinib

Product 1

HCID 16006490Nilotinib Hydrochloride AnhydrousYield 95%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Conditions

Temperature
55 °C

Procedure

To 1 Liter reactor was added Nilotinib-base form A (20 g, 0.04 mol), absolute ethanol (188 ml) and 13.77% HCl solution in ethanol abs. (10 g, 0.04 mol). The slurry was heated to reflux, mild dissolution occurred during the stirring, and the mixture was filtered under reduced pressure. During the filtration precipitation occurred. The precipitate was returned to the reactor. The mixture was heated to reflux until dissolution occurred at 65° C. and then cooled gradually to 55° C. During cooling, the solution precipitated at 60° C. The slurry was heated to reflux and cooled for 3 hours to 5° C. The slurry stirred at 5° C. over night, and ethanol abs. was added (100 ml) before filtration. The material filtered, washed with ethanol abs., and dried over night at 70° C. in vacuum oven to yield Nilotinib-HCl form T17 (19 g, 95% yield).

Workup

  1. temperatureThe slurry was heated
  2. temperatureto reflux
  3. dissolutionmild dissolution
  4. filtrationthe mixture was filtered under reduced pressure
  5. filtrationDuring the filtration precipitation
  6. temperatureThe mixture was heated
  7. temperatureto reflux until dissolution
  8. customoccurred at 65° C.
  9. temperatureDuring cooling
  10. customthe solution precipitated at 60° C
  11. temperatureThe slurry was heated
  12. temperatureto reflux
  13. temperaturecooled for 3 hours to 5° C
  14. additionwas added (100 ml)
  15. filtrationbefore filtration
  16. filtrationThe material filtered
  17. washwashed with ethanol abs
  18. custom, and dried over night at 70° C. in vacuum oven

Sources & evidence

ORD record
ord-d3a348b41a714c32b4b014356dbbef28
Source dataset
uspto-grants-2013_11
Patent number
US08592442B2

Reaction notes

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